systemic disorders with corneal changes

1. SYSTEMIC
DISORDERS WITH
CORNEAL
CHANGES
P R E S E N T E R : D R . I D D I N D YA B A W E
M O D U L ATO R : D R . K A L I N A K I A B U B A K A R

2. OUTLINE
• Disorders of Carbohydrate metabolism
• Disorders of lipid metabolism and storage
• Disorders of amino acid metabolism
• Disorders of protein metabolism
• Disorders of Immunoglobulin synthesis
• Non-inflammatory disorders of connective tissue
• Disorders of Nucleotide Metabolism
• Disorders of Mineral Metabolism

3. DISORDERS OF CARBOHYDRATE
METABOLISM
• Mucopolysaccharidoses
• Diabetes Mellitus

4. MUCOPOLYSACCHARIDOSES
• rare, inherited lysosomal storage diseases
• can cause corneal clouding from the accumulation of incompletely degraded GAGs
within the keratocytes, corneal epithelium, and endothelium, and also within the
extracellular matrix of the cornea
• Incidence: 1 in 10,000 births.

5. .

6. PATHOGENESIS:
• At present, at least 8 MPS syndromes have been described, all of which are autosomal
recessive, with the exception of Hunter syndrome, which is X-linked.
• the three "MPS I" disorders (Hurler, Scheie, and Hurler-Scheie) result from different
amino acid substitutions that result in a defect in a-L-iduronidase.
• Hurler syndrome (MPS I-H) is the most severe of the the three, severe cognitive
impairment and with corneal clouding appearing by 1 year of age.

7. CLINICAL FINDINGS:
• Corneal clouding
• Retinopathy
• Optic atrophy
• LAB EVAL: Urine for GAGs. Leukocyte or plasma enzyme assay most precise
• Mgt: PK…

8. HURLER

9. DIABETES MELLITUS .”
• PATHOGENESIS: accum of sorbitol alters epi and endo. Leading to thickening of
multilaminar basement membrane, reduced hemidesmosomes and decreased
penetration of anchoring fibrils…. These affect epi-stromal adhesion
• Reduced corneal nerve density and nerve branching related to degree of DM
neuropathy
• CLINICAL FINDINGS: corneal epi surf changes, hypoesthesia
• LAB EVAL: Glycosylated hem related to poor DM control…. Could point to poor
corneal healing
• MGT: Lubs, avoid toxic meds, using therapeutic CLs, minimize epi debridement
surgery, manage Meibomian gland dysfunction, PK

10. DISORDERS OF LIPID METABOLISM
AND STORAGE
• Hyperlipoproteinemias
• Hypolipoproteinemias
• Shingolipidoses
• Mucolipidoses

11. HYPERLIPOPROTEINEMIAS
• Assoc: premature coronary artery and peripheral vascular disease
• Ocular hallmarks: xanthelasma, corneal arcus
• Pathogenesis: extracellular deposits of cholesterol, triglycerides, phospholipids
• O/E: Corneal arcus… in <40yr olds!!!
• LAB EVAL: Fasting and alcohol-restricted lipid profile.
• MGT: Refer for dietary or drug treatment

12. HYPOLIPOPROTEINEMIAS
• 5 disorders: LCAT deficiency, Tangier dx, fish eye dx, familial hypobetalipoproteinemia,
Bassen-Kornzweig syndrome. 3….”
• O/E: LCAT has peripheral arcus and nebular stromal haze. Fish eye dx has corneal
clouding from minute gray-white-yellow dots. Tangier dx has very large orange tonsils;
enlarged liver, spleen and lymph nodes. Corneas have diffuse clouding and opacities
but no arcus.
• LAB EVAL and MGT: Serum lipid profile shows low HDL (lowest in Tangier’s dz).
Appropriate referral and genetic counselling

13. SHINGOLIPIDOSES
• 4 conditions: Fabry dz, multiple sulfatase deficiency, generalized gangliosidosis, Tay
Sachs dz
• Pathogenesis: Fabry caused by deficiency of a-galactosidase A causing accum of
ceramide trihexoside in renal and cardiovascular systems.
• Clinical findings: whorl-like lines in basal layers of corneal epithelium, periorbital edema
(25%), cataracts. Corneal changes resemble those on long-term chloroquine or
amiodarone
• LAB EVAL: In Fabry dz, a-galactosidase A level is markedly decreased in urine and
plasma.

14. .

15. MUCOLIPIDOSES
• AR conditions with features common to MPS and lipidoses
• Pathogenesis: inherited disroders of carbohydrate and lipid metabolism combined.
MPS accum in cornea and viscera.
• Dz in this class: ML1, ML2, ML3, ML4, Goldenberg syndrome, mannosidosis,
fucosidosis. {Chr,19.
• O/E: corneal clouding except in mannosidosis and fucosidosis.
• LAB EVAL: Plasma lysosomal hydrolases elevated.
• MGT: Both PK and lamellar keratoplasty (LK) have poor results; allograft limbal stem
cell transplant an option

16. DISORDERS OF AMINO ACID
METABOLISM

17. .

18. DISORDERS OF PROTEIN
METABOLISM
• Amyloidosis: extracellular accum of amyloid deposits in various tissues and organs
including cornea and conjunctiva.
• Primary localized amyloidosis is the most common form of ocular amyloidosis
• Primary systemic amyloidosis: waxy ecchymotic eyelid papules assoc with vitreaous
veils and opacitites
• Secondary localized amyloidosis: most common form of amyloidosis of the cornea.
• Secondary systemic amyloidosis: seen in many conditions like RA. Amyloid doesn’t
deposit in the cornea in secondary systemic amyloidosis

19. .

20. DISORDERS OF IMMUNOGLOBULIN
SYNTHESIS
• Watch in MM, WM, BMG.. Have excess synthesis of Ig by plasma cells; assoc with
crystalline corneal deposits
• Pathogenesis: direct tissue invasion or hyperviscosity syndrome
• O/E: Crystalline deposition in all layers of cornea, copper deposition in cornea,
sludging of blood flow in conjunctiva and retina, pars plana proteinaceous cysts,
infiltration of sclera, orbital bony invasion with proptosis.
• LAB EVAL: Serum electrophoresis, CBC and general screening for albumin/globulin
and Ca2+ levels,
• Mgt: No ophthal Rx needed except when depositions interfere with vision… LK

21. NON-INFLAMMATORY DISORDERS OF
CONNECTIVE TISSUE
• Ehlers-Danlos Syndrome: hyperextensibility of joints and skin, easy bruisability and
formation of “cigarette paper” scars.
• Pathogenesis: AD, AR, and X-linked variants. 20 types. Specific defects occur in collagen
type I and III synthesis, and there can be lysyl hydroxylase deficiency.
• Clinical findings: EDS type VI is ocular-scoliotic type, AR, assoc with only moderate joint and
skin extensibility, brittle cornea easily ruptured on minor trauma, blue sclera, keratoconus
keratoglobus and severe scoliosis.
• Lab eval: altered urinary ratio of lysysl pyridinoline to hydroxylysyl pyridinoline that is x-tic of
EDS VI.
• MGT: Be aware of condition and associations: MVP
, SBR, ..brittle cornea mimics child
abuse!!!.. Use patch grafts to repair corneoscleral ruptures. Genetic counselling

22. MARFAN SYNDROME
• Common AD disorder associated with disorders of the eye (ectopia lentis), heart and
skeletal system. Maps to fibrillin gene.
• Pathogenesis: defects in fibrillin synthesis
• O/E: thinning of sclera, subluxation of lens, flattening of cornea
• Mgt: Complete cardiac eval. CTR during cataract surgery in case of lens subluxation.

23. DISORDERS OF NUCLEOTIDE
METABOLISM
• Gout: results from deposition of urate crystals in the joints or kidney
• Pathogenesis: RFs… obesity, cytotoxic chemotherapy, myeloproliferative disease,
diuretic therapy, excessive alcohol intake
• O/E: fine corneal epithelial and stromal deposits . Rarely an orange-brown band
keratopathy or typical whitish band keratopathy
• LAB EVAL: Serum uric acid level typically elevated.
• Mgt: Indomethacin, Colchicine or phenylbutazone… allopurinol… superficial deposits
can be scrapped off or keratectomy done

24. PORPHYRIA
• Excess production and excretion of porphyrins, pigments involved in synthesis of heme
• Pathogenesis: Porphyria cutanea tarda, form most commonly associated with ocular
surface disease. Is sporadic or AD.
• o/e: corneal thinning and perforation at limbus
• Lab eval: urine turns dark on standing. Reduced liver and red cell uroporphyrinogen
decarboxylase activity is confirmatory.
• Mgt: protection from UV light and reduction of iron by phlebotomy or subcut
desferrioxamine are the principal treatments. No specific ocular treatment. Artificial
tears helfpful.

25. DISORDERS OF MINERAL
METABOLISM
• Wilson disease: (hepatolenticular degeneration).
An AR disorder caused by multiple allelic substitutions or deletions in an ATPase,
Pathogenesis: Copper deposited in liver, then in kidneys and eventually in brain and
cornea at Descemet membrane.
O/E: Copper deposition in posterior Descemet membrane (Kayser-Fleischer ring).
Gonioscopy helpful in seeing this ring.
Lab eval: low serum ceruloplasmin, high urinary copper suggestive of dx
Mgt: Penicillamine. KF ring used to monitor progress of therapy.

26. REFERENCE
• AAO Bk 8 (2016-2017)